Ulcerative colitis (UC) is a chronic intermittent and relapsing inflammatory bowel disease (IBD) of the colon characterized by superficial mucosal lesions that extend through the rectum and progress upstream. The natural history of UC is characterized by the progression of colonic lesions in up to 50% of subjects. This suggests that the colonic mucosa has a “global” susceptibility to environmental factors, but etiology of UC remains unknown and current treatments are limited as 30% of patients require colectomy. Human studies identified unbalanced endoplasmic reticulum stress (ERS) in unaffected colonic mucosa from UC patients1,2. Animal models in which ERS is disrupted are highly sensitive to chemically-induced colitis 2-6 or develop intestinal inflammation 2,7-9 suggesting that unbalanced ERS give rise to inflammation. However, there are no ERS-regulating strategies proposed in the management of UC in part by the lack of adequate experimental model mimicking UC.